European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology · 2026
Modified nodal staging for intrahepatic cholangiocarcinoma invading hilum and perihilar cholangiocarcinoma.
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Wei Tao, Zhang Jian, Guo Shouliang, Chatzipanagiotou Odysseas P, Zhang Xu-Feng, Guglielmi Alfredo, Weiss Matthew, Popescu Irinel, Ratti Francesca, Marques Hugo P, Aucejo Federico, Maithel Shishir K, Shen Feng, Pulitano Carlo, Poultsides George A, Koerkamp Bas Groot, Itaru Endo, Lesurtel Mickael, Martel Guillaume, Kitago Minoru, Gleisner Ana, Bauer Todd W, Pawlik Timothy M, Intrahepatic and Perihilar Cholangiocarcinoma Study Group
Аннотация
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) encompasses a heterogenous group of malignancies. Hilar type iCCA (h-iCCA) may represent a distinct subtype characterized by invasion of the hepatic hilum. We sought to investigate the clinicopathological characteristics of h-iCCA with a focus on the prognostic impact of nodal status relative to peripheral iCCA and perihilar cholangiocarcinoma (pCCA).
METHODS: Patients with iCCA and pCCA undergoing curative-intent resection were identified from an international multi-institutional database. Prognostic impact of different lymph node metastasis (LNM) count in each subtype of iCCA and pCCA were examined, and a modified N category was proposed.
RESULTS: Among 1240 patients with iCCA, 291 (23.5%) had tumors with hilar invasion; h-iCCA was associated with more aggressive clinicopathological characteristics and worse prognosis. Patients with h-iCCA were more likely to undergo lymphadenectomy and had an increased likelihood of LNM. Among h-iCCA, patients with 1-2 LNM had worse OS versus individuals without nodal metastasis (median OS: 24.0 vs. 53.9 months; p < 0.001), yet better OS compared with individuals with ≥ 3 LNM (median OS: 24.0 vs. 15.0 months; p = 0.039). In contrast, patients with peripheral iCCA with 1-2 LNM and ≥ 3 LNM had comparable OS (median OS: 29.0 vs. 26.5 months, p = 0.472). Patients with h-iCCA and pCCA with no nodal metastasis, 1-2 LNM, and≥ 3 LNM had incrementally worse OS. h-iCCA demonstrated a divergent genomic landscape compared with peripheral iCCA, with a higher frequency of KRAS and TP53 mutations yet lower incidence of IDH mutation; genomic alterations were largely concordant between h-iCCA versus pCCA.
CONCLUSIONS: iCCA with hilar invasion represented a distinct subgroup of CCA characterized by aggressive behavior and poor survival that had clinical and genetic features more consistent with pCCA than peripheral iCCA. A modified N category is proposed for h-iCCA and pCCA: mN0 (no nodal metastasis), mN1 (1-2 LNM), and mN2 (≥3 LNM), which provided better discrimination for patient prognosis.
METHODS: Patients with iCCA and pCCA undergoing curative-intent resection were identified from an international multi-institutional database. Prognostic impact of different lymph node metastasis (LNM) count in each subtype of iCCA and pCCA were examined, and a modified N category was proposed.
RESULTS: Among 1240 patients with iCCA, 291 (23.5%) had tumors with hilar invasion; h-iCCA was associated with more aggressive clinicopathological characteristics and worse prognosis. Patients with h-iCCA were more likely to undergo lymphadenectomy and had an increased likelihood of LNM. Among h-iCCA, patients with 1-2 LNM had worse OS versus individuals without nodal metastasis (median OS: 24.0 vs. 53.9 months; p < 0.001), yet better OS compared with individuals with ≥ 3 LNM (median OS: 24.0 vs. 15.0 months; p = 0.039). In contrast, patients with peripheral iCCA with 1-2 LNM and ≥ 3 LNM had comparable OS (median OS: 29.0 vs. 26.5 months, p = 0.472). Patients with h-iCCA and pCCA with no nodal metastasis, 1-2 LNM, and≥ 3 LNM had incrementally worse OS. h-iCCA demonstrated a divergent genomic landscape compared with peripheral iCCA, with a higher frequency of KRAS and TP53 mutations yet lower incidence of IDH mutation; genomic alterations were largely concordant between h-iCCA versus pCCA.
CONCLUSIONS: iCCA with hilar invasion represented a distinct subgroup of CCA characterized by aggressive behavior and poor survival that had clinical and genetic features more consistent with pCCA than peripheral iCCA. A modified N category is proposed for h-iCCA and pCCA: mN0 (no nodal metastasis), mN1 (1-2 LNM), and mN2 (≥3 LNM), which provided better discrimination for patient prognosis.